Collins has a hairline medial malleolus stress fracture, according to the team, and a date for surgery has yet to be determined.
Collins had averaged seven points and 6.3 rebounds in 11 games this season.
He had missed most of the 2019-20 season after having left shoulder surgery, but he returned for the NBA's restart in Lake Buena Vista, Florida, and helped the Blazers reach the Western Conference playoffs with a play-in victory over the Memphis Grizzlies.
Collins leaves the Blazers -- who are tied 1-1 in an opening-round playoff series with the Los Angeles Lakers -- more vulnerable on the front line against L.A.'s size and skill.
Portland lost forward Rodney Hood to a season-ending Achilles injury and forward Trevor Ariza to a restart opt-out for family considerations, and has been without first-round pick Nassir Little in the playoffs.